The aim of this study was to investigate the combined influence of 3 independent variables in the preparation of piroxicam proniosomes by the slurry method. A 3-factor, 3-level Box-Behnken design was used to derive a second-order polynomial equation and construct contour plots to predict responses. The independent variables selected were molar ratio of Span 60:cholesterol (X(1)), surfactant loading (X(2)), and amount of drug (X(3)). Fifteen batches were prepared by the slurry method and evaluated for percentage drug entrapment (PDE) and vesicle size. The transformed values of the independent variables and the PDE (dependent variable) were subjected to multiple regression to establish a full-model second-order polynomial equation. F was calculated to confirm the omission of insignificant terms from the full-model equation to derive a reduced-model polynomial equation to predict the PDE of proniosome-derived niosomes. Contour plots were constructed to show the effects of X(1), X(2) and X(3) on the PDE. A model was validated for accurate prediction of the PDE by performing checkpoint analysis. The computer optimization process and contour plots predicted the levels of independent variables X(1), X(2), and X(3) (0, -0.158 and -0.158 respectively), for maximized response of PDE with constraints on vesicle size. The Box-Behnken design demonstrated the role of the derived equation and contour plots in predicting the values of dependent variables for the preparation and optimization of piroxicam proniosomes.

Abstract. The purpose of this study was to evaluate the effect of formulation components on the in vitro skin permeation of microemulsion drug delivery system containing fluconazole (FLZ). Lauryl alcohol (LA) was screened as the oil phase of microemulsions. The pseudo-ternary phase diagrams for microemulsion regions were constructed using LA as the oil, Labrasol (Lab) as the surfactant and ethanol (EtOH) as the cosurfactant. The formulation which showed a highest permeation rate of 47.15± 1.12 µg cm −2 h −1 and appropriate physicochemical properties was optimized as containing 2% FLZ, 10%LA, 20% Lab/EtOH (1:1), and 68% double-distilled water (w/w). The efficiency of microemulsion formulation in the topical delivery of FLZ was dependent upon the contents of water and LA as well as Lab/EtOH mixing ratio. It was concluded that the percutaneous absorption of FLZ from microemulsions was enhanced with increasing the LA and water contents, and with decreasing the Lab/EtOH ratio in the formulation. Candida albicans was used as a model fungus to evaluate the antifungal activity of the best formula achieved, which showed the widest zone of inhibition as compared to FLZ reference. The studied microemulsion formulation showed a good stability for a period of 3 months. These results indicate that the studied microemulsion formulation might be a promising vehicle for topical delivery of FLZ.

The purpose of this study was to evaluate the effect of oil, surfactant/co-surfactant mixing ratios and water on the in vitro permeation of ketoconazole (KTZ) applied in O/W microemulsion vehicle through intact rat skin. Lauryl Alcohol (LA) was screened as the oil phase of microemulsions, due to a good solubilizing capacity of the microemulsion system. The pseudo-ternary phase diagrams for microemulsion regions were constructed using LA as the oil, Labrasol (Lab) as the surfactant (S) and ethanol (EtOH) as the cosurfactant (CoS). The formulation which showed a highest permeation rate of 54.65 ± 1.72 µg/cm(2)/h(1) and appropriate physico-chemical properties was optimized as containing 2% KTZ, 10% LA, 20% Lab/EtOH (1:1) and 68% double distilled water (w/w). The efficiency of microemulsion formulation in the topical delivery of KTZ was dependent upon the contents of water and LA as well as Lab/EtOH mixing ratio. It was concluded that the percutaneous absorption of KTZ from microemulsions was enhanced with increasing the LA and water contents, and with decreasing the Lab/EtOH ratio in the formulation. Candida albicans was used as a model fungus to evaluate the antifungal activity of the best formula achieved, which showed the widest zone of inhibition as compared to KTZ reference. The studied microemulsion formulation showed a good stability for a period of three months. Histopathological investigation of rat skin revealed the safety of microemulsion formulations for topical use. These results indicate that the studied microemulsion formulation might be a promising vehicle for topical delivery of KTZ.

The objective of the present investigation was to improve the dissolution rate of Rofecoxib (RXB), a poorly water-soluble drug by solid dispersion technique using a water-soluble carrier, Poloxamer 188 (PXM). The melting method was used to prepare solid dispersions. A 3 2 full factorial design approach was used for optimization wherein the temperature to which the melt-drug mixture cooled (X 1 ) and the drug-to-polymer ratio (X 2 ) were selected as independent variables and the time required for 90% drug dissolution (t 90 ) was selected as the dependent variable. Multiple linear regression analysis revealed that for obtaining higher dissolution of RXB from PXM solid dispersions, a low level of X 1 and a high level of X 2 were suitable. The differential scanning calorimetry and x-ray diffraction studies demonstrated that enhanced dissolution of RXB from solid dispersion might be due to a decrease in the crystallinity of RXB and PXM and dissolution of RXB in molten PXM during solid dispersion preparation. In conclusion, dissolution enhancement of RXB was obtained by preparing its solid dispersions in PXM using melting technique. The use of a factorial design approach helped in identifying the critical factors in the preparation and formulation of solid dispersion.

The present study was carried out with a view to enhance the dissolution of poorly water-soluble BCS-class II drug aceclofenac by co-grinding with novel porous carrier Neusilin US(2.) (amorphous microporous granules of magnesium aluminosilicate, Fuji Chemical Industry, Toyama, Japan). Neusilin US(2) has been used as an important pharmaceutical excipient for solubility enhancement. Co-grinding of aceclofenac with Neusilin US(2) in a ratio of 1:5 was carried out by ball milling for 20 h. Samples of co-ground mixtures were withdrawn at the end of every 5 h. and characterized for X-ray powder diffraction, differential scanning calorimetry, and Fourier-transform infrared spectroscopy. The analysis revealed the conversion of crystalline aceclofenac to its amorphous form upon milling with Neusilin US(2). Further, in vitro dissolution rate of aceclofenac from co-ground mixture was significantly higher compared to pure aceclofenac. The accelerated stability study of co-ground mixture was carried out at 40 degrees C/75%RH for 4 weeks, and it showed that there was no reversion from amorphous to crystalline form. Thus, it is advantageous to use a porous carrier like Neusilin US(2) in improvement of dissolution of poorly soluble drugs.